The ability of animals to survive food deprivation is an adaptive response accompanied by the atrophy of many tissues and organs to minimize energy expenditure. This atrophy and its reversal following the return to a normal diet involves stem cell-based regeneration in the hematopoietic and nervous systems (Brandhorst et al., 2015; Cheng et al., 2014). However, whether prolonged fasting and refeeding can also cause pancreatic regeneration and/or cellular reprogramming leading to functional lineage development is unknown. β cells residing in pancreatic islets are among the most sensitive to nutrient availability. Whereas Type 1 and type 2 diabetes (T1D and T2D) are characterized by β-cell dedifferentiation and trans-differentiation (Cnop et al., 2005, Dor and Glaser, Talchai et al., 2012; Wang et al.), β-cell reprogramming, proliferation and/or stepwise re-differentiation from pluripotent cells are proposed as therapeutic interventions (Baeyens et al., 2014; Chera et al., 2014; Maehr et al., 2009; Pagliuca et al., 2014; Sneddon et al., 2012; Zhou et al., 2008), suggesting that lineage-conversion is critical in both diabetes pathogenesis and therapy (Weir et al., 2013).
Although the dietary intervention with the potential to ameliorate insulin resistance and Type II diabetes have been studied extensively for decades, whether these have the potential to promote a lineage-reprogramming reminiscent of that achieved by iPSCs-based engineering remains unknown. We previously showed that cycles of prolonged fasting (2-3 days) can protect mice and humans from toxicity associated with chemotherapy and promote hematopoietic stem cell-dependent regeneration (Cheng et al., 2014; Laviano and Rossi Fanelli; Piran et al., 2014; Raffaghello et al., 2008).
Accordingly, there is an ongoing need for methods of promoting cell regeneration.